Prolylendopeptidase is an example of endopeptidase and exhibits an activity of inactivating the following substances: substance P which is a neuro-conducting substance; thyrotropin-releasing hormone; neurotensin; and vasopressin which seems to have a relation with memories. It is considered that prolylendopeptidase inhibitor substances might have various physiological activities. Particularly, it is observed that a prolylendopeptidase inhibitor substance exhibits an action of inhibiting an inactivation of vasopressin, so that it is expected that this substance might be useful as medicine for the treatment of amnestic syndromes. For instance, Journal of the Japanese Agricultural Chemical Society, 58, 1147-1154 (1984) and Japanese Patent Publication (Laid-open) Nos. 60-172929 (1985) and 60-188317 (1985) disclose that certain prolylendopeptidase inhibitor agents show an anti-amnestic effect. So, it is highly desirable to provide a more effective prolylendopeptidase inhibitor agent which can be used as an anti-amnestic agent.
It is reported by Aoyagi that, from the experimental data concerning the enzyme activity in spleens of NZB/WF1 mice suffering from SLE (systematic lupus erythematosus), it can be said that the amount of prolylendopeptidase increases with a progress of the sick (Journal of Applied Biochemistry, 7, 273-281 (1985)). It is therefore expected that a prolylendopeptidase inhibitor agent might be effective for the treatment of SLE.
It is also known that there are a number of low molecular weight peptidase having an endopeptidase-inhibiting activity. Examples of such low molecular weight peptides are natural peptide aldehydes such as leupeptin and elastatinal. Furthermore, a number of peptide aldehydes have been synthesized as endopeptidase inhibitor agents. According to a theory proposed by Thompson, R. C. (Biochemistry, 12, 47-51 (1973)), such peptide aldehydes are bonded to enzymes, so that the aldehyde radicals of the peptide aldehydes may occupy the sites of the enzymes where they can react with the carbonyl radicals of (substrate) peptide, so as to inhibit the enzyme activity.
Hori et al reported that certain peptides, having an (RS)-3-amino-2-oxo-pentanoic acid ethyl or benzyl ester radical at the C-terminal, can be prepared by a Dakin-West reaction, and that these synthetic peptides inhibit the activity of elastase, which is an example of peptidases (Peptides, Structure and Function, Proceedings of the Ninth American Peptide Symposium, pp. 819-822 (1985)).